Osteoarthritis (OA) is a debilitating condition in which the articular cartilage becomes damaged, eventually causing pain and leading to a reduction in joint function. OA involves both anabolic and catabolic events, however, the stimulus for many of these events in unknown. It has been shown in humans, and in animal models, that OA involves both cartilage and subchondral bone changes, but the question remains as to the exact relationship between the two. It has been suggested that a thickened (stiffened) subchondral bone is less capable of absorbing forces at the joint and, therefore, transmits greater force to the overlying articular cartilage, which becomes damaged. The cartilaginous changes occurring in OA (both in humans and in animal models) have been much better characterized than the bony changes. The applicant will utilize an establish a rabbit model of chymopapain-induced cartilage damage to study the subchondral bone changes and the relationship between these bone changes and the articular cartilage changes. Morphological and biochemical analysis of the bone and cartilage will set the baseline for the study of the relationship between the two. In this model, subchondral bone changes are controlled (by a proven bone remodelling inhibitor, alendronate) and the question is raised what will be the effect on the cartilage damage? The Specific Aims of the proposal are: 1) to determine the effect of inhibition of subchondral bone remodelling, through the action of alendronate, on the overlying AC after a high dose chymopapain injury; 2) to describe the changes and levels of select body fluid metabolic markers of bone and cartilage after a chymopapain injury, with and without alendronate treatment, and to correlate these changes with morphological appearance of the AC and subchondral bone at two time points; and 3) to describe the subchondral bone morphology after a chymopapain injury, with or without alendronate treatment. The working hypothesis is that the inhibition of bone remodelling in a rabbit model of OA will limit the degradation of the overlying articular cartilage.